Regional nodal irradiation is not associated with significantly reduced locoregional recurrence rates in node-positive breast cancer with a favorable risk


Regional nodal irradiation is not associated with significantly reduced locoregional recurrence rates in node-positive breast cancer with a favorable risk

The addition of regional nodal irradiation (RNI) to a patient’s treatment regimens did not significantly reduce locoregional recurrence rates (LRRs) in patients with favorable-risk, node-positive hormone receptor-positive, HER2-negative breast cancer, according to findings from the Phase 3 SWOG S1007 RxPONDER trial (NCT01272037) published in JAMA Oncology.1

At a median follow-up of 6.1 years, findings from the secondary analysis showed that patients who underwent breast conserving surgery and radiotherapy with RNI (n = 1522), breast conserving surgery with radiotherapy (n = 1397), mastectomy with postmastectomy radiotherapy (n = 901), and mastectomy without radiotherapy (n = 760) had 5-year LRRs of 0.85%, 0.5 5%, 0.11% and 1.7% respectively. In addition, invasive disease-free survival (iDFS) was not affected by the presence or absence of RNI in premenopausal patients (HR, 1.03; 95% CI, 0.74-1.43; P = 0.87) or postmenopausal (HR, 0.85; 95% CI, 0.68-1.07; P = .16).1

Additional findings from the analysis showed that predictors of RNI receipt after breast conserving surgery included having a tumor size of T3 versus T1 (OR, 2.80; 95% CI, 1.70-4.63; P < .001), with 2 positive nodes versus 1 (OR, 1.67; 95% CI, 1.40-2.00; P < .001), and with 3 positive nodes versus 1 (OR, 2.76; 95% CI, 2.00-3.79; P < .001). Similarly, predictors of receiving radiotherapy after mastectomy included having a tumor size of T3 versus T1 (OR, 9.02; 95% CI, 5.58-14.57; P < 0.001), with 2 positive nodes versus 1 (OR, 1.60; 95% CI, 1.27-2.01; P < 0.001), and with 3 positive nodes versus 1 (OR, 3.18; 95% CI, 2.25-4.51; P < .001).1

Patients who were premenopausal had a lower incidence of locoregional recurrence when undergoing breast conserving surgery plus radiotherapy compared to mastectomy alone (HR, 0.41; 95% CI, 0.19-0.91; P = .03); this trend was also true in postmenopausal women (HR, 0.48; 95% CI, 0.20-1.13; P = .09).

iDFS in premenopausal women was significantly improved for patients who underwent breast conserving surgery plus radiotherapy without RNI versus mastectomy (HR, 0.60; 95% CI, 0.37-0.95; P = .03). None of the other treatment combinations compared to mastectomy without radiotherapy produced a significant benefit in terms of iDFS in premenopausal or postmenopausal women.

Primary results of the trial, which were published in the New England Journal of Medicineshowed in 2021 that adding chemotherapy to endocrine therapy did not confer a major iDFS benefit in the overall population; the 5-year iDFS rates were 92.2% versus 91.0% in patients in the chemoendocrine (n = 2487) and endocrine arm (n = 2497), respectively (HR, 0.86; 95% CI, 0.72-1.03; P= .10). However, premenopausal patients experienced a significant benefit in terms of iDFS with chemoendocrine therapy compared to endocrine therapy alone (HR, 0.60; 95% CI, 0.43-0.83; P= .002).2

To perform the secondary analysis of S1007 published in JAMA Oncologyresearchers used a prospective radiotherapy data collection form to collect data on radiotherapy receipt, targets, and dose for patients enrolled in the study.1 RNI was defined based on an indication of treatment targets that included at least the supraclavicular region. Researchers also described receiving radiotherapy to the internal breast, in addition to conducting a sensitivity analysis that considered an alternative definition of RNI, including targeting node regions.1

Multivariable logistic regression models were then constructed using the following independent variables: menopausal status (premenopausal versus postmenopausal), sentinel node biopsy versus axillary dissection, tumor size (T1, T2, or T3), number of positive lymph nodes (1, 2, or 3), and recurrence score. Radiotherapy information was recorded in the first year after random assignment. The findings were analyzed from June 2022 to April 2023.1

Patients eligible in SWOG S1007 RxPONDER were required to have non-inflammatory disease without distant metastases, undergo primary surgery with sentinel lymph node biopsy or axillary lymph node dissection, and be able to undergo a taxane and/or anthracycline regimen.2

Patients were randomly assigned 1:1 to be treated with chemoendocrine therapy or chemotherapy alone. The primary endpoint was iDFS, secondary endpoints were distant recurrence-free survival and overall survival.2

The analysis collected data from a total of 4871 female patients with a median age of 57 years (range 18-87). Patients in breast conserving surgery and radiotherapy with RNI, breast conserving surgery with radiotherapy, mastectomy plus radiotherapy and mastectomy alone underwent endocrine monotherapy at rates of 49.9%, 52.3%, 49.1% and 53.0%, respectively. Most patients in each arm were postmenopausal (69.9% vs 70.0% vs 58.1% vs 65.6%), had 1 positive node (60.5% vs 76.3% vs 53.4% ​​vs 69.2%), and had a recurrence score of 14 to 25 (57.5% vs 57.1% vs 55.6% vs 58.2%).1

The study authors concluded by noting that these findings highlight the need to evaluate when to omit RNI for this patient population “…these findings provide valuable information in suggesting that further investigation of RNI omission in this population is worthwhile and that chemotherapy omission in patients similar to those enrolled on S1007 is not itself an independent indication for the use of RNI. These findings reinforce the need for prospective studies of optimal locoregional management and radiotherapy field design in patients with limited nodal load and favorable biology, they wrote in conclusion.1

References

  1. Jagsi R, Barlow WE, Woodward WA, et al. Use of radiotherapy and incidence of locoregional recurrence in patients with node-positive breast cancer at favorable risk enrolled in the SWOG S1007 trial. JAMA Oncol. Published online July 6, 2023. doi:10.1001/jamaoncol.2023.1984
  2. Kalinsky K, Barlow WE, Gralow JR, et al. 21 gene test to inform the benefit of chemotherapy in node-positive breast cancer. N Engl J Med. 2021;385(25):2336-2347. doi:10.1056/NEJMoa2108873


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